The coupling of aryl compounds to form biaryl compounds or polyaryl compounds via carbon-carbon bonds is of great synthetic importance. A large number of methods are known to effect such couplings, including Ullman couplings of aryl iodides and bromides (see P. E. Fanta, "The Ullman Synthesis of Biaryls," Synthesis, 9, 9-21, 1974), coupling of aryl bromides and iodides with aryl boronic acids and esters using palladium catalysts (A. Suzuki, Acc. Chem. Res., 15, 178, 1982), reductive coupling of aryl halides with magnesium via Grignard reagents using nickel catalysts (T. Yamamoto and A. Yamamoto, Chem. Left., 353-356, 1977), reductive coupling of aryl chlorides with zinc using nickel triphenylphosphine catalysts (I. Colon and D. R. Kelsey, J. Org. Chem., 51, 2627-2637, 1986; and U.S. Pat. No. 4,326,989) and oxidative coupling of phenols using iron (III) or air and copper catalysts (L. F. Fieser and M. Fieser, Reagents for Organic Synthesis, Vol. 1, 390, 1967).
Each of the above-referenced prior art methods for the coupling of aryl compounds has certain limitations. The Ullman coupling generally results in low yields and, for best results, requires aryl iodides, which are expensive. Although coupling of aryl chlorides, which are less expensive than aryl iodides and aryl bromides, has been accomplished by Yamamoto et al via Grignard reagents, the generally more expensive aryl bromides and iodides are preferred. In addition, in the Yamamoto et al coupling reactions, groups such as ketones and esters, which are not stable to Grignard conditions, must be avoided, thereby limiting the scope of useful reactions. While the Suzuki coupling is the method of choice for cross-coupling to form asymmetric biaryls, it uses expensive palladium catalysts and boronic acid substrates, which makes the process more expensive and, hence, less desirable.
Because aryl chlorides cost substantially less than aryl bromides and aryl iodides, the nickel phosphine catalyzed couplings disclosed by Colon et al are widely used. In the Colon et al method, a nickel compound, salt, or complex is reduced in situ with zinc powder in the presence of a phosphine (specifically a triaryl phosphine) to form an active nickel (O) phosphine catalyst. It is theorized that in the triarylphosphine process, each of the nickel species in the catalytic cycle is capable of losing one or more of its phosphine ligands (L) to form coordinatively unsaturated complexes. These equilibria have been studied by Tolman (C. A. Tolman, W. C. Seidel, and L. W. Gosser, J. Am. Chem., 96, 53 (1974)). The formation f unsaturated complexes is said to be essential at certain parts of the cycle, so that the aryl halide may react. However, during other parts of the cycle, unsaturated nickel complexes may cause the formation of unwanted by-products or may react to form inert complexes unable to catalyze further coupling. It has been found in using the Colon et al process that the concentration of phosphine ligand must be kept between certain limits to prevent the formation of unsaturated nickel complexes which are too reactive and which lead to unwanted side reactions. The typical range of concentrations is approximately 0.2 to 0.5 M triphenylphosphine, 0.5 to 1 M aryl halide, and 0.01 to 0.05 M nickel.
In view of the foregoing, it can be seen that in the Colon et al. process relatively large amounts of triphenylphosphine must be used in coupling reactions compared to the amount of aryl halide substrate. Since such large amounts of triphenylphosphine must be used, recovery and purification of triphenylphosphine is required to enhance process economics. Because of the inefficiencies involved in the recovery, the cost of the process is substantially increased.
In addition to the increased cost of the Colon et al process due to the loss of triphenylphosphine, such processes also result in unwanted by-products due to abstraction of an aryl group (Ar') from the phosphine P(Ar').sub.3. The abstracted aryl group can couple to aryl halide (ArX), giving an undesired by-product Ar--Ar', for example. While increasing the concentration of phosphine ligand can suppress (but not eliminate) this undesired side reaction, increasing the phosphine concentration further increases the loss of triphenylphosphine, thereby increasing the overall process cost.
Aryl sulfonates react in a fashion similar to aryl halides and may be coupled using nickel phosphine catalysts such as that of Colon et al., for example, see the work of Percec et al. (V. Percec, J-Y. Bae, M. Zhao, and D. H. Hill, J. Org. Chem., 1995, 60, 176-185; and U.S. Pat. No. 5,241,044, issued Aug. 31, 1993.)
There is a need in the art for economical catalyst systems which can be used in reactions which couple aryl halides or aryl sulfonates to form either biaryl or polyaryl compounds and which enhance the economics of the process while reducing or substantially eliminating by-product formation.